The parent project for this FIRCA application is a large, ongoing multicenter project that has as its goal the assembly of 2,000 patients with probable or definite Alzheimer Disease (AD) in order to study family history, medical history, epidemiologic data, and genotype patients for apolipoprotein E (ApoE)and other genetic markers. The aims of the parent project are to assess gene-gene interaction on risk of AD, specifically by estimating the proportion of genetic variability in AD susceptibility accounted for by APOE and ascertain likely genetic models for other common AD susceptibility genes; and to assess gene- environment interaction on risk of AD, by evaluating the joint effects of APOE, MGAD (major gene for AD) probability, gender, age, and factors such as smoking, education, and anti-inflammatory drugs) on AD risk. They also plan to identify factors which enable an individual to survive to age 90 without succumbing to AD. The goals of the FIRCA grant are to develop additional genetic markers/polymorphisms in candidate genes, including PSEN1, PSEN2, APP, mitochondrial cytochrome oxidase, and APOE, to evaluate them in familial and non-familial AD subjects, to identify novel genes and search for polymorphisms or mutations which may promote an AD pathway, and to evaluate their interaction with other factors on AD risk and phenotypic variation. The ethnically diverse Russian population of AD patients will be sampled from the AD Center in the Mental Health Research Center in Moscow, Russia.